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Even higher blow-up of
part of the Chr 7 physical map of variation in App expression in brain. The QTL region actually extends from
about 119 to 129.
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Notes:
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1. As mentioned
in the previous slide another important approach to ranking candidates is
based on the number of sequence variants that distinguish the parental
strains. If we were sure that the sequences of the gene, its promoter, and
its enhancers were identical between the strains then we could discount--but
not eliminate--that gene as a candidate. The Gtf3c1 candidate almost falls
into this category: of 663 known SNPs in and around this gene, only four
differ between C57BL/6J and DBA/2J. Gtf3c1 is essentially
identical-by-descent in these strains and is a less likely candidate. In
contrast, if the two alleles of the gene have dozens of functional variants
in exons, promoters, enhancers, and splice sites, then it becomes a higher
priority candidate.
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Of course it
only takes a single critical sequence variant to generate downstream
effects. The argument above is really about the prior probabilities. Where
would you place your bets given the information at hand?
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2. If you scroll down the INTERVAL
ANALYST you will find that Ctbp2 is a particularly interesting candidate
that contains lots of SNPs (n = 75 and a SNP density of 0.55 SNP/Kb). Ctbp2
is also closer to our QTL peak than was Gtf3c1. Not only does Ctbp2 contain
lots of SNPs but it is also is associated with a powerful cis QTL with an
LRS of 24.2 (divide by 4.61 to get the equivalent LOD score of 5.25).
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3. At this high magnification,
individual genes are distinct. They are color coded by their density of
SNPs. Bright orange represents those genes that have a high SNP density
(C57BL/6J versus DBA/2J), black represents genes with low SNP density. Roll
the cursor over a gene block and its name will pop up, along with
information on exon number.
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4. Beneath the physical map you will
find an INTERVAL ANALYST table that lists information on known genes in the
region on which you have zoomed the Physical Map.
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5. As always: error-checking is
important. Some genes may be missing from the Interval Analyst (recent
additions or errors of omission). In this case the Zranb1 gene that is
located just proximal to Ctbp2 is not listed in the INTERVAL ANALYST.
Double-check the interval using the Genome Browser links (blue and beige
horizontal bars) at the top of the PHYSICAL MAP.
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